Introduction

The earliest reports of hemochromatosis recognized involvement of the endocrine system in this condition; diabetes mellitus was the first recorded endocrine disorder. With wider recognition of hemochromatosis, involvement of other endocrine glands was suspected and early reports emphasized the occurrence of hypogonadism. Diagnosis at that time was based solely on clinical features, though in some instances was supported by histological data obtained at autopsy. In 1935, Sheldon described in detail the occurrence of sexual hypoplasia presenting as ‘loss of hair and impotence with atrophic testes and the body showing feminine characteristics.’ He suggested that this clinical syndrome was the most frequent manifestation of hemochromatosis, after the classical triad of diabetes mellitus, hepatomegaly, and pigmentation. Since then, other endocrinopathies have been reported in association with hemochromatosis, though none with the frequency of hypogonadism.

In the foregoing account, the non-diabetic endocrinopathies associated with hemochromatosis are discussed. There are profound differences in the relative frequency with which the various glands are affected. This may simply be a function of the severity and duration of iron deposition. However, one might question this hypothesis, bearing in mind the severity of iron deposition seen in certain glands, notably the thyroid and parathyroids, whose function seems rarely to be affected. However, there may be a variability in the vulnerability of different secretory cells to the toxic effects of iron. The reason for this is not apparent, nor is it clear why iron deposition should be more severe in some glands than in others. At present, methods for quantifying iron in endocrine cells is relatively imprecise, and improved methods may be informative.